tbuckley/cabot-search huggingface dataset:
Intranasal COVID-19 Vaccine Disappointing in First-in-Human Trial
Authors: Anita Slomski
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Oncogenic FOXL2 C134W Mutation Is a Key Driver of Granulosa Cell Tumors
Authors: Elena Llano, Anne Laure Todeschini, Natalia Felipe-Medina, María D. Corte-Torres, Yazmine B. Condezo, Manuel Sanchez-Martin, Sara López-Tamargo, Aurora Astudillo, Xose S. Puente, Alberto M. Pendas, Reiner A. Veitia
Journal: Cancer Research (2022)

Abstract Adult-type granulosa cell tumors (AGCT) are the most common type of malignant ovarian sex cord–stromal tumors. Most AGCTs carry the somatic variant c.402C&amp;gt;G (p.C134W) affecting the transcription factor FOXL2. Germline dominant variants in FOXL2 are responsible for blepharophimosis syndrome, which is characterized by underdevelopment of the eyelid. In this work, we generated a mouse model harboring the C134W variant of FOXL2 to evaluate in vivo the poorly understood oncogenic role of FOXL2. The mutation was dominant regarding eyelid hypoplasia, reminiscent of blepharophimosis syndrome. Interestingly, Foxl2+/C134W female mice had reduced fertility and developed AGCTs through a progression from abnormal ovaries with aberrant granulosa cells to ovaries with stromal hyperplasia and atypia and on to tumors in adut mice. The genes dysregulated in mouse AGCTs exhibited the hallmarks of cancer and were consistent with a gain-of-function of the mutated allele affecting TGFβ signaling. A comparison of these data with previous results on human AGCTs indicated similar deregulated pathways. Finally, a mutational analysis of mouse AGCT transcriptomic data suggested the absence of additional driver mutations apart from FOXL2-C134W. These results provide a clear in vivo example in which a single mutational hit triggers tumor development associated with profound transcriptomic alterations. Significance: A newly generated mouse model carrying a FOXL2 mutation characteristic of adult-type granulosa cell tumors shows that FOXL2 C134W shifts the transcriptome towards a signature of granulosa cell cancer and drives tumorigenesis.
Gender Differences in Emergency Medicine Attending Physician Comments to Residents: A Qualitative Analysis
Authors: Mira Mamtani, Frances Shofer, Kevin Scott, Dana Kaminstein, Whitney Eriksen, Michael Takacs, Andrew K. Hall, Anna Weiss, Lauren A. Walter, Fiona Gallahue, Lainie Yarris, Stephanie B. Abbuhl, Jaya Aysola
Journal: JAMA Network Open (2022)

Importance Prior studies have revealed gender differences in the milestone and clinical competency committee assessment of emergency medicine (EM) residents. Objective To explore gender disparities and the reasons for such disparities in the narrative comments from EM attending physicians to EM residents. Design, Setting, and Participants This multicenter qualitative analysis examined 10 488 narrative comments among EM faculty and EM residents between 2015 to 2018 in 5 EM training programs in the US. Data were analyzed from 2019 to 2021. Main Outcomes and Measures Differences in narrative comments by gender and study site. Qualitative analysis included deidentification and iterative coding of the data set using an axial coding approach, with double coding of 20% of the comments at random to assess intercoder reliability (κ, 0.84). The authors reviewed the unmasked coded data set to identify emerging themes. Summary statistics were calculated for the number of narrative comments and their coded themes by gender and study site. χ 2 tests were used to determine differences in the proportion of narrative comments by gender of faculty and resident. Results In this study of 283 EM residents, of whom 113 (40%) identified as women, and 277 EM attending physicians, of whom 95 (34%) identified as women, there were notable gender differences in the content of the narrative comments from faculty to residents. Men faculty, compared with women faculty, were more likely to provide either nonspecific comments (115 of 182 [63.2%] vs 40 of 95 [42.1%]), or no comments (3387 of 10 496 [32.3%] vs 1169 of 4548 [25.7%]; P &amp;amp;lt; .001) to men and women residents. Compared with men residents, more women residents were told that they were performing below level by men and women faculty (36 of 113 [31.9%] vs 43 of 170 [25.3%]), with the most common theme including lack of confidence with procedural skills. Conclusions and Relevance In this qualitative study of narrative comments provided by EM attending physicians to residents, multiple modifiable contributors to gender disparities in assessment were identified, including the presence, content, and specificity of comments. Among women residents, procedural competency was associated with being conflated with procedural confidence. These findings can inform interventions to improve parity in assessment across graduate medical education.
How I treat Elderly Patients with DLBCL in the frontline setting.
Authors: Pieternella J Lugtenburg, Pim G.N.J. Mutsaers
Journal: Blood (2022)

Diffuse large B-cell lymphoma (DLBCL) is an aggressive but potentially curable disease and is most common in older people. Rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard of care for fit patients without cardiac contraindications. In each individual elderly patient the potential gains of treatment should be balanced against the risks of treatment related morbidity and mortality. A simplified comprehensive geriatric assessment or easily performed assessments such as gait speed and grip strength can be helpful to assess the fitness of an elderly patient. Pre-phase with corticosteroids, rigorous supportive care including G-CSF prophylaxis and careful monitoring can be important to prevent adverse events. In unfit elderly patients a dynamic dosing strategy is often applied. For very elderly patients (≥ 80 years) a dose reduced regimen (R-miniCHOP) is recommended. When anthracyclines are contraindicated, doxorubicin can be replaced by etoposide or gemcitabine. Most frail patients do not benefit from chemotherapy. Further progress can be expected from non-chemotherapy based therapies, such as bispecific antibodies, antibody-drug conjugates and immunomodulatory agents. This article provides an overview of first line treatment in elderly patients with DLBCL and our approach to the management of these challenging patients.
Inhaled particulate accumulation with age impairs immune function and architecture in human lung lymph nodes
Authors: Basak B. Ural, Daniel P. Caron, Pranay Dogra, Steven B. Wells, Peter A. Szabo, Tomer Granot, Takashi Senda, Maya M. L. Poon, Nora Lam, Puspa Thapa, Yoon Seung Lee, Masaru Kubota, Rei Matsumoto, Donna L. Farber
Journal: Nature Medicine (2022)
<i>HER2</i> Copy Number and Resistance Mechanisms in Patients with HER2-positive Advanced Gastric Cancer Receiving Initial Trastuzumab-based Therapy in JACOB Trial
Authors: Filippo Pietrantonio, Paolo Manca, Sara Erika Bellomo, Simona Corso, Alessandra Raimondi, Enrico Berrino, Federica Morano, Cristina Migliore, Monica Niger, Lorenzo Castagnoli, Serenella Maria Pupa, Caterina Marchiò, Maria Di Bartolomeo, Eleonora Restuccia, Chiara Lambertini, Josep Tabernero, Silvia Giordano
Journal: Clinical Cancer Research (2022)

Abstract Purpose: In JACOB trial, pertuzumab added to trastuzumab-chemotherapy did not significantly improve survival of patients with HER2-positive metastatic gastric cancer, despite 3.3 months increase versus placebo. HER2 copy-number variation (CNV) and AMNESIA panel encompassing primary resistance alterations (KRAS/PIK3CA/MET mutations, KRAS/EGFR/MET amplifications) may improve patients’ selection for HER2 inhibition. Experimental Design: In a post hoc analysis of JACOB on 327 samples successfully sequenced by next-generation sequencing (NGS; Oncomine Focus DNA), HER2 CNV, HER2 expression by IHC, and AMNESIA were correlated with overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) by univariable/multivariable models. Results: Median HER2 CNV was 4.7 (interquartile range, 2.2–16.9). HER2 CNV-high versus low using the median as cutoff was associated with longer median PFS (10.5 vs. 6.4 months; HR = 0.48; 95% confidence interval: 0.38–0.62; P &amp;lt; 0.001) and OS (20.3 vs. 13.0 months; HR = 0.54; 0.42–0.72; P &amp;lt; 0.001). Combining HER2 CNV and IHC improved discriminative ability, with better outcomes restricted to HER2-high/HER2 3+ subgroup. AMNESIA positivity was found in 51 (16%), with unadjusted HR = 1.35 (0.98–1.86) for PFS; 1.43 (1.00–2.03) for OS. In multivariable models, only HER2 CNV status remained significant for PFS (P &amp;lt; 0.001) and OS (P = 0.004). Higher ORR was significantly associated with IHC 3+ [61% vs. 34% in 2+; OR = 3.11 (1.89–5.17)] and HER2-high [59% vs. 43% in HER2-low; OR = 1.84 (1.16–2.94)], with highest OR in the top CNV quartile. These biomarkers were not associated with treatment effect of pertuzumab. Conclusions: HER2 CNV-high assessed by NGS may be associated with better ORR, PFS, and OS in a JACOB subgroup, especially if combined with HER2 3+. The negative prognostic role of AMNESIA requires further clinical validation.
Use of Albumin Solution in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass—Reply
Authors: Eero Pesonen, Tatu Juvonen, Ville Pettilä
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Dyspnea—When a Sensation Becomes a Symptom
Authors: Richard M. Schwartzstein
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
White House Fixes “Family Glitch” in Health Insurance Subsidies
Authors: Melissa Suran
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<scp>Cell‐Mediated</scp> Cytotoxicity in Lyme Arthritis
Authors: David Ordóñez, Robert B. Lochhead, Klemen Strle, Annalisa Pianta, Sheila Arvikar, Ildiko Van Rhijn, Anat Stemmer‐Rachamimov, Allen C. Steere
Journal: Arthritis & Rheumatology (2022)

Obliterative microvascular lesions are found in the synovial tissue of ~50% of patients with post-antibiotic Lyme arthritis (LA) and correlate with autoantibodies to certain vascular antigens. In this study, we identified lymphocytes with cytotoxic potential that may also mediate this feature of synovial pathology.
Glioblastoma immuno-endothelial multicellular microtissue as a 3D in vitro evaluation tool of anti-cancer nano-therapeutics
Authors: Cláudia Martins, Catarina Pacheco, Catarina Moreira-Barbosa, Ângela Marques-Magalhães, Sofia Dias, Marco Araújo, Maria J. Oliveira, Bruno Sarmento
Journal: Journal of Controlled Release (2022)

Despite being the most prevalent and lethal type of adult brain cancer, glioblastoma (GBM) remains intractable. Promising anti-GBM nanoparticle (NP) systems have been developed to improve the anti-cancer performance of difficult-to-deliver therapeutics, with particular emphasis on tumor targeting strategies. However, current disease modeling toolboxes lack close-to-native in vitro models that emulate GBM microenvironment and bioarchitecture, thus partially hindering translation due to poorly predicted clinical responses. Herein, human GBM heterotypic multicellular tumor microtissues (MCTMs) are generated through high-throughput 3D modeling of U-251 MG tumor cells, tissue differentiated macrophages isolated from peripheral monocytes, and brain microvascular primary endothelial cells. GBM MCTMs mimicked tumor spatial organization, extracellular matrix production and necrosis areas. The bioactivity of a model drug, docetaxel (DTX), and of tumor-targeted DTX-loaded polymeric NPs with a surface L-Histidine moiety (H-NPs), were assessed in the MCTMs. MCTMs cell uptake and anti-proliferative effect was 8- and 3-times higher for H-NPs, respectively, compared to the non-targeted NPs and to free DTX. H-NPs provided a decrease of MCTMs anti-inflammatory M2-macrophages, while increasing their pro-inflammatory M1 counterparts. Moreover, H-NPs showed a particular biomolecular signature through reduced secretion of an array of medium cytokines (IFN-γ, IL-1β, IL-1Ra, IL-6, IL-8, TGF-β). Overall, MCTMs provide an in vitro biomimetic model to recapitulate key cellular and structural features of GBM and improve in vivo drug response predictability, fostering future clinical translation of anti-GBM nano-therapeutic strategies.
US Tracking System for Nonfatal Drug Overdoses—Reply
Authors: Rahul Gupta, David R. Holtgrave
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease
Authors: Henne Holstege, Marc Hulsman, Camille Charbonnier, Benjamin Grenier-Boley, Olivier Quenez, Detelina Grozeva, Jeroen G. J. van Rooij, Rebecca Sims, Shahzad Ahmad, Najaf Amin, Penny J. Norsworthy, Oriol Dols-Icardo, Holger Hummerich, Amit Kawalia, Philippe Amouyel, Gary W. Beecham, Claudine Berr, Joshua C. Bis, Anne Boland, Paola Bossù, Femke Bouwman, Jose Bras, Dominique Campion, J. Nicholas Cochran, Antonio Daniele, Jean-François Dartigues, Stéphanie Debette, Jean-François Deleuze, Nicola Denning, Anita L. DeStefano, Lindsay A. Farrer, Maria Victoria Fernández, Nick C. Fox, Daniela Galimberti, Emmanuelle Genin, Johan J. P. Gille, Yann Le Guen, Rita Guerreiro, Jonathan L. Haines, Clive Holmes, M. Arfan Ikram, M. Kamran Ikram, Iris E. Jansen, Robert Kraaij, Marc Lathrop, Afina W. Lemstra, Alberto Lleó, Lauren Luckcuck, Marcel M. A. M. Mannens, Rachel Marshall, Eden R. Martin, Carlo Masullo, Richard Mayeux, Patrizia Mecocci, Alun Meggy, Merel O. Mol, Kevin Morgan, Richard M. Myers, Benedetta Nacmias, Adam C. Naj, Valerio Napolioni, Florence Pasquier, Pau Pastor, Margaret A. Pericak-Vance, Rachel Raybould, Richard Redon, Marcel J. T. Reinders, Anne-Claire Richard, Steffi G. Riedel-Heller, Fernando Rivadeneira, Stéphane Rousseau, Natalie S. Ryan, Salha Saad, Pascual Sanchez-Juan, Gerard D. Schellenberg, Philip Scheltens, Jonathan M. Schott, Davide Seripa, Sudha Seshadri, Daoud Sie, Erik A. Sistermans, Sandro Sorbi, Resie van Spaendonk, Gianfranco Spalletta, Niccolo’ Tesi, Betty Tijms, André G. Uitterlinden, Sven J. van der Lee, Pieter Jelle Visser, Michael Wagner, David Wallon, Li-San Wang, Aline Zarea, Jordi Clarimon, John C. van Swieten, Michael D. Greicius, Jennifer S. Yokoyama, Carlos Cruchaga, John Hardy, Alfredo Ramirez, Simon Mead, Wiesje M. van der Flier, Cornelia M. van Duijn, Julie Williams, Gaël Nicolas, Céline Bellenguez, Jean-Charles Lambert
Journal: Nature Genetics (2022)

Abstract Alzheimer’s disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70% 1 . The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants 2 . Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals—16,036 AD cases and 16,522 controls. Next to variants in TREM2 , SORL1 and ABCA7 , we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10 . Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD.
Interstitial Lung Disease With Non–Vitamin K Oral Anticoagulants—A Clinical Concern?
Authors: Emanuel Raschi
Journal: JAMA Network Open (2022)

Yi-Hsin Chan, MD; Tze-Fan Chao, MD, PhD; Shao-Wei Chen, MD, PhD; Hsin-Fu Lee, MD; Wei-Min Chen, MS; Pei-Ru Li, BS; Yung-Hsin Yeh, MD; Chi-Tai Kuo, MD; Lai-Chu See, PhD; Gregory Y. H. Lip, MD
Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect
Authors: Yoko Nishiga, Alexandros P. Drainas, Maya Baron, Debadrita Bhattacharya, Amira A. Barkal, Yasaman Ahrari, Rebecca Mancusi, Jason B. Ross, Nobuyuki Takahashi, Anish Thomas, Maximilian Diehn, Irving L. Weissman, Edward E. Graves, Julien Sage
Journal: Nature Cancer (2022)

Radiation therapy is a mainstay of cancer treatment but does not always lead to complete tumor regression. Here we combine radiotherapy with blockade of the 'don't-eat-me' cell-surface molecule CD47 in small cell lung cancer (SCLC), a highly metastatic form of lung cancer. CD47 blockade potently enhances the local antitumor effects of radiotherapy in preclinical models of SCLC. Notably, CD47 blockade also stimulates off-target 'abscopal' effects inhibiting non-irradiated SCLC tumors in mice receiving radiation. These abscopal effects are independent of T cells but require macrophages that migrate into non-irradiated tumor sites in response to inflammatory signals produced by radiation and are locally activated by CD47 blockade to phagocytose cancer cells. Similar abscopal antitumor effects were observed in other cancer models treated with radiation and CD47 blockade. The systemic activation of antitumor macrophages following radiotherapy and CD47 blockade may be particularly important in patients with cancer who suffer from metastatic disease.